Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Sep 1;89(17):8040–8044. doi: 10.1073/pnas.89.17.8040

Characterization of a metabotropic glutamate receptor: direct negative coupling to adenylyl cyclase and involvement of a pertussis toxin-sensitive G protein.

L Prezeau 1, O Manzoni 1, V Homburger 1, F Sladeczek 1, K Curry 1, J Bockaert 1
PMCID: PMC49851  PMID: 1355603

Abstract

We have characterized a G-protein-coupled glutamate receptor in primary cultures of striatal neurons. Glutamate, quisqualate, or trans-1-aminocyclopentane-1,3-dicarboxylate inhibited by 30-40% either forskolin-stimulated cAMP production in intact cells or forskolin plus vasoactive intestinal peptide-activated adenylyl cyclase assayed in neuronal membrane preparations. These inhibitory effects were suppressed after treatment of striatal neurons with Bordetella pertussis toxin, suggesting the involvement of a heterotrimeric guanine nucleotide-binding protein (G protein) of the G(i)/G(o) subtype. The pharmacological profile of this glutamate receptor negatively coupled to adenylyl cyclase was different from that of the metabotropic Qp glutamate receptor coupled to phospholipase C in striatal neurons and from that of the recently cloned "mGluR2" glutamate receptor, which is negatively coupled to adenylyl cyclase when expressed in non-neuronal cells.

Full text

PDF
8040

Images in this article

8043Image
on p.8043
8043Image
on p.8043

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baskys A., Malenka R. C. Trans-ACPD depresses synaptic transmission in the hippocampus. Eur J Pharmacol. 1991 Jan 25;193(1):131–132. doi: 10.1016/0014-2999(91)90213-a. [DOI] [PubMed] [Google Scholar]
  2. Bonner T. I. The molecular basis of muscarinic receptor diversity. Trends Neurosci. 1989 Apr;12(4):148–151. doi: 10.1016/0166-2236(89)90054-4. [DOI] [PubMed] [Google Scholar]
  3. Brabet P., Dumuis A., Sebben M., Pantaloni C., Bockaert J., Homburger V. Immunocytochemical localization of the guanine nucleotide-binding protein Go in primary cultures of neuronal and glial cells. J Neurosci. 1988 Feb;8(2):701–708. doi: 10.1523/JNEUROSCI.08-02-00701.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Charpak S., Gähwiler B. H., Do K. Q., Knöpfel T. Potassium conductances in hippocampal neurons blocked by excitatory amino-acid transmitters. Nature. 1990 Oct 25;347(6295):765–767. doi: 10.1038/347765a0. [DOI] [PubMed] [Google Scholar]
  5. Curry K., Peet M. J., Magnuson D. S., McLennan H. Synthesis, resolution, and absolute configuration of the isomers of the neuronal excitant 1-amino-1,3-cyclopentanedicarboxylic acid. J Med Chem. 1988 Apr;31(4):864–867. doi: 10.1021/jm00399a030. [DOI] [PubMed] [Google Scholar]
  6. Fagni L., Bossu J. L., Bockaert J. Activation of a Large-conductance Ca2+-Dependent K+ Channel by Stimulation of Glutamate Phosphoinositide-coupled Receptors in Cultured Cerebellar Granule Cells. Eur J Neurosci. 1991;3(8):778–789. doi: 10.1111/j.1460-9568.1991.tb01674.x. [DOI] [PubMed] [Google Scholar]
  7. Gusovsky F., Gutkind J. S. Selective effects of activation of protein kinase C isozymes on cyclic AMP accumulation. Mol Pharmacol. 1991 Feb;39(2):124–129. [PubMed] [Google Scholar]
  8. Houamed K. M., Kuijper J. L., Gilbert T. L., Haldeman B. A., O'Hara P. J., Mulvihill E. R., Almers W., Hagen F. S. Cloning, expression, and gene structure of a G protein-coupled glutamate receptor from rat brain. Science. 1991 May 31;252(5010):1318–1321. doi: 10.1126/science.1656524. [DOI] [PubMed] [Google Scholar]
  9. Manzoni O. J., Finiels-Marlier F., Sassetti I., Blockaert J., le Peuch C., Sladeczek F. A. The glutamate receptor of the Qp-type activates protein kinase C and is regulated by protein kinase C. Neurosci Lett. 1990 Feb 5;109(1-2):146–151. doi: 10.1016/0304-3940(90)90553-l. [DOI] [PubMed] [Google Scholar]
  10. Manzoni O. J., Poulat F., Do E., Sahuquet A., Sassetti I., Bockaert J., Sladeczek F. A. Pharmacological characterization of the quisqualate receptor coupled to phospholipase C (Qp) in striatal neurons. Eur J Pharmacol. 1991 Jul 12;207(3):231–241. doi: 10.1016/0922-4106(91)90035-g. [DOI] [PubMed] [Google Scholar]
  11. Manzoni O., Fagni L., Pin J. P., Rassendren F., Poulat F., Sladeczek F., Bockaert J. (trans)-1-amino-cyclopentyl-1,3-dicarboxylate stimulates quisqualate phosphoinositide-coupled receptors but not ionotropic glutamate receptors in striatal neurons and Xenopus oocytes. Mol Pharmacol. 1990 Jul;38(1):1–6. [PubMed] [Google Scholar]
  12. Manzoni O., Prezeau L., Sladeczek F., Bockaert J. Trans-ACPD inhibits cAMP formation via a pertussis toxin-sensitive G-protein. Eur J Pharmacol. 1992 Apr 10;225(4):357–358. doi: 10.1016/0922-4106(92)90112-9. [DOI] [PubMed] [Google Scholar]
  13. Masu M., Tanabe Y., Tsuchida K., Shigemoto R., Nakanishi S. Sequence and expression of a metabotropic glutamate receptor. Nature. 1991 Feb 28;349(6312):760–765. doi: 10.1038/349760a0. [DOI] [PubMed] [Google Scholar]
  14. Miller R. J. Metabotropic excitatory amino acid receptors reveal their true colors. Trends Pharmacol Sci. 1991 Oct;12(10):365–367. doi: 10.1016/0165-6147(91)90604-q. [DOI] [PubMed] [Google Scholar]
  15. Monaghan D. T., Bridges R. J., Cotman C. W. The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system. Annu Rev Pharmacol Toxicol. 1989;29:365–402. doi: 10.1146/annurev.pa.29.040189.002053. [DOI] [PubMed] [Google Scholar]
  16. Nawy S., Jahr C. E. Suppression by glutamate of cGMP-activated conductance in retinal bipolar cells. Nature. 1990 Jul 19;346(6281):269–271. doi: 10.1038/346269a0. [DOI] [PubMed] [Google Scholar]
  17. Peralta E. G., Ashkenazi A., Winslow J. W., Ramachandran J., Capon D. J. Differential regulation of PI hydrolysis and adenylyl cyclase by muscarinic receptor subtypes. Nature. 1988 Aug 4;334(6181):434–437. doi: 10.1038/334434a0. [DOI] [PubMed] [Google Scholar]
  18. Salomon Y., Londos C., Rodbell M. A highly sensitive adenylate cyclase assay. Anal Biochem. 1974 Apr;58(2):541–548. doi: 10.1016/0003-2697(74)90222-x. [DOI] [PubMed] [Google Scholar]
  19. Schoepp D. D., Johnson B. G., Monn J. A. Inhibition of cyclic AMP formation by a selective metabotropic glutamate receptor agonist. J Neurochem. 1992 Mar;58(3):1184–1186. doi: 10.1111/j.1471-4159.1992.tb09381.x. [DOI] [PubMed] [Google Scholar]
  20. Schoepp D., Bockaert J., Sladeczek F. Pharmacological and functional characteristics of metabotropic excitatory amino acid receptors. Trends Pharmacol Sci. 1990 Dec;11(12):508–515. doi: 10.1016/0165-6147(90)90052-a. [DOI] [PubMed] [Google Scholar]
  21. Sladeczek F., Pin J. P., Récasens M., Bockaert J., Weiss S. Glutamate stimulates inositol phosphate formation in striatal neurones. Nature. 1985 Oct 24;317(6039):717–719. doi: 10.1038/317717a0. [DOI] [PubMed] [Google Scholar]
  22. Sladeczek F., Récasens M., Bockaert J. A new mechanism for glutamate receptor action: phosphoinositide hydrolysis. Trends Neurosci. 1988 Dec;11(12):545–549. doi: 10.1016/0166-2236(88)90183-x. [DOI] [PubMed] [Google Scholar]
  23. Tanabe Y., Masu M., Ishii T., Shigemoto R., Nakanishi S. A family of metabotropic glutamate receptors. Neuron. 1992 Jan;8(1):169–179. doi: 10.1016/0896-6273(92)90118-w. [DOI] [PubMed] [Google Scholar]
  24. Weiss S., Pin J. P., Sebben M., Kemp D. E., Sladeczek F., Gabrion J., Bockaert J. Synaptogenesis of cultured striatal neurons in serum-free medium: a morphological and biochemical study. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2238–2242. doi: 10.1073/pnas.83.7.2238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Weiss S., Sebben M., Garcia-Sainz J. A., Bockaert J. D2-dopamine receptor-mediated inhibition of cyclic AMP formation in striatal neurons in primary culture. Mol Pharmacol. 1985 Jun;27(6):595–599. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES